Programmable solid phase extraction and elution device

ABSTRACT

An automated, integrated system for programmably selectively extracting and purifying one or more particular solutes from a contaminated solution, said purified solutes then being recovered as a concentrated solution suitable for analysis.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.07/788,578, filed Nov. 6, 1991, which is a continuation-in-part of U.S.patent application Ser. No. 07/488,306, filed Mar. 5, 1990, both nowabandoned.

FIELD OF THE INVENTION

The present invention relates to devices adapted to process a liquidhaving one or more solutes dissolved therein by causing said liquid tocontact a solid extractant or sorbent to remove said solutes and moreparticularly to programmable systems adapted to meter a preselectedamount of said liquid from a selected storage container and transfersaid metered liquid to one or more programmably selectable receptaclescontaining said solid sorbent for said solute removal and theconcentration of said removed solute for subsequent recovery.

BACKGROUND OF THE INVENTION

Liquid/liquid extraction is a laboratory and industrial technique forseparating a dissolved solute from a solution thereof which has been inuse for many years. Such method comprises one or more steps in which afirst liquid solution of a solute in a first, relatively non-volatile,solvent is vigorously mixed with a second, usually organic, solvent. Thesecond solvent, while having a high affinity for the solute material, isboth much more volatile than the first solvent and substantiallyimmiscible therewith. Recovery of the solute is accomplished byseparating the two liquids and then evaporating the second solvent toallow the recovery of the solute therefrom. Such method, whilerelatively simple to perform, suffers from the disadvantage that themost suitable volatile solvents are materials such as hexane, benzene,ether, acetone, methyl chloride, acetonitrile and chloroform. All ofthese materials present substantial flammable and/or toxic hazards sothat proper handling and recovery constitutes an ever more stringent setof environmental and economic problems. In extreme cases, the costs ofdisposing of these materials can be anywhere from 5 to 10 times theinitial cost of the organic solvent. Further, when such an approach isused, for example, in the testing of urine or blood samples for one ormore drugs, the relatively long times required for such an extractioncauses serious problems in many high-volume analytical laboratories.With all of this, it has been reported that, as recently as 1984, of the400 million plus analytical samples prepared and tested in the nation'sbiological, clinical, pharmaceutical, toxicological, forensic,environmental, chemical, food and cosmetic laboratories, over 60 percentwere still prepared by liquid/liquid extraction.

One emerging technology being used to overcome these problems is knownas solid phase extraction. Using this method, the first solutioncontaining solvent is passed through a cartridge containing a selectedsolid inorganic or organic sorbent phase to extract the solute from thesolvent. One typical sorbent material for this purpose is an ionexchange resin which removes dissolved salts of calcium, iron andsimilar mineral material from water in many household and industrialwater softener units. In many cases, the desired product is usually the"softened" water. In these units the resin is rejuvenated byperiodically backflushing the resin bed with a salt solution anddiscarding the flush solution to a public sewer. In other cases, theextracted mineral material is of interest, and the backflush solution isretained in the system to recover the dissolved solute. While many largeunits based on this technique can be found in industry, there has notbeen a concomitant development of special, relatively small, automatedunits utilizing this approach to meet the needs of forensic, toxicology,clinical and other high volume analytical laboratories.

SUMMARY OF THE INVENTION

The present invention comprises an automated, integrated programmablesystem which provides for use of a solid sorbent to accomplish the rapidextraction and concentration of organic and/or inorganic solutes fromdilute solutions thereof and then the recovery of said concentratedsolute for analysis or other use. As used herein the terms"programmably" or "programmable" mean an operation conducted under thecontrol of a computer or controller. In the present invention, thesorbent is a solid phase material, such as an organic resin, which isselected as being especially suitable for removing the dissolved soluteof interest. Further, all operations relating to the processing of thefluids, from the initial conditioning of the sorbent in cartridgereceiver tubes, the placing of the raw materials in the receiver tubes,the metering of the treatment fluids from one or more solutioncontainers to one or more selected cartridge receiver tubes, to thefinal elution and removal of the concentrated solute from one or moreselected cartridge receiver tubes are performed in a fully integratedsystem in which all process steps are performed under the instructionsdelivered from a central programmable controller or computer. The systemis further adapted to process a plurality of raw input solutions and toprovide a multiplicity of output concentrates of one or more extractedsolutes from these raw solutions. Such capability is made possible bythe incorporation of special multi-port valves which are adapted toallow the transfer of all solutions, as set up in the controller, fromselected one(s) of the solution/solvent containers to selected one(s) ofthe receiver tubes. In use, such a system is found to be over ten timesfaster and costing only about 1/10th as much as conventionalliquid/liquid extraction. Further, the quantities of materials subjectto one or more environmental controls can be considerably reduced.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention, there is shown in thedrawings forms which are presently preferred; it being understood,however, that the invention is not limited to the precise arrangementsand instrumentalities shown.

FIG. 1 is a simplified diagrammatic representation showing the principalexternal features of the present invention.

FIG. 2 is a plan view of an extractant receiver tube and extractantcartridge used in the present invention.

FIGS. 3a and 3b are schematic diagrams showing the general electricaland mechanical relationships, respectively, of the principal elements ofthe present invention.

FIG. 4 is a front view of a multi-port valve rotary disk member used inthe present invention.

FIG. 5 is a sectional view of the multi-port valve rotary disk membertaken along line 5--5 of FIG. 4.

FIG. 6 is a diagrammatic representation of the general mode of using thepresent invention to extract a particular solute from a solution sample.

FIG. 7 is a simplified diagrammatic representation showing analternative embodiment of the principal external features of the presentinvention.

FIG. 8 is a monitor display screen for a test run to be performed by theembodiment of FIG. 7.

FIGS. 9a to 9d illustrate process status display screens as generated bythe test run in the embodiment of FIG. 7.

FIG. 10 is a display screen showing the sample locations for the testsolutions used in the test run illustrated in FIG. 8.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description is of the best presently contemplatedmodes of carrying out the present invention. This description is notintended in a limiting sense, but is made solely for the purpose ofillustrating the general principals of the invention.

Referring now to the drawings in detail, wherein like numbers representlike elements, there is shown in FIG. 1 the principal external featuresof the system of the present invention in a simplified diagrammaticrepresentation of the basic flow path of fluid materials therethrough.In the center is process unit 10 which contains, within housing 12, allof the individual units, along with their associated electrical andplumbing connections, which are used to meter and control the flow offluids into, through, and out of the system. On the front of the upperprojection of housing 12 is an alpha-numeric display 14, number keypad16 and function select keypad 18, the functions of which will beexplained below. In the embodiment illustrated, process unit 10 isadapted to receive treatment solutions of desired fluids from aplurality of solution containers (for the purpose of this illustrationthe number of solution containers or receptacles is 12), collectively20. Also shown is stand 22 which, as shown, is adapted to support,position, and retain a plurality of cartridge receiver tubes,collectively 24, firmly in place under the outlet taps (not shown)within the confines of the process unit 10. Also within the confines ofstand 22 is an outlet adapted to receive discharged fluids and conveythem either to a waste storage receptacle (not shown) or to a series ofeluted sample containers (also not shown) corresponding in number andplacement to the receiver tubes.

In the particular embodiment shown, the containers 20 are used to supplyboth the raw fluid material (such as contaminated water, blood or urine)from which a solute is to be extracted and one or more solvents and washsolutions used in the resulting process. These solvents and washsolutions are used to remove any contaminants, such as residual rawsolution adhering to the extracted solute and/or achieving the finalelution and concentration of the solute after it has been extracted fromthe raw solution. Suitable solvents and wash solution materials includewater, methanol, acetonitrile, ethyl acetate, chloroform, toluene,hexane, and dilute NaOH, saline and acid solutions. When the testmaterial is a fluid, the upper segment of the process unit 10 (whichoverhangs the stand 22) is pivoted upward and one or more aliquotsamples of the raw test material or fluid is pippetted into selectedones of the cartridge receiver tubes 24. Prior to such placing of theraw test fluid in the cartridge receiver tubes 24, one or more of thesolutions stored within containers 20 may be used to pretreat orcondition the sorbent material in the selected receiver tubes 24.Thereafter, the system operating procedure is configured to causealiquot portions of the same and other solutions to be metered from thecontainers 20 for further processing at the appropriate times.

Although the described embodiment can cause containers 20 toautomatically supply the fluid raw materials or samples to the receivertubes 24, manually introducing the raw fluid material offers severaladvantages. For example, this procedure does not present any potentialproblems with contaminating the system fluid lines and connections. Thisapproach allows the introduction of the raw fluid samples into as manyas thirty (30) cartridge receiver tubes 24 by having the system operatorpippette requisite aliquot portions of the samples directly into thereceiver tubes 24 after they have been conditioned with one or moresolvents. This manual introduction of the samples also permits a greaternumber of containers to be used for storage of a larger variety oftreatment solutions and solvents for use in extracting the solutes froma variety of sample solutions and materials.

Moreover, the system is not limited to processing liquid samplesolutions. Solid materials, if properly shredded or granulated may alsobe processed. These materials can be processed merely by first placing aweighed amount of the solid material into each of the cartridge receivertubes 24 being used (after appropriate conditioning), repositioning theupper segment of the process unit 10 over stand 22, and then adjustingthe process schedule to achieve the desired results.

In the embodiment illustrated, the processing of the sampled solution(s)can be conducted, simultaneously, in as many as thirty (30) of thecartridge receiver tubes 24. Here too, it should be appreciated thatfacilities able to accommodate larger or smaller numbers of samplingcontainers 20 or cartridge receiver tubes 24 may be used withoutaffecting the scope of the present invention.

Entering into the rear of housing 12 is the inlet tube 26 for a gassupply (not shown), the purpose of which will be explained below. Alsonot shown are a plurality of inert, preferably Teflon, hollow fluidtransfer tubes, one coming from each of sample containers 20 toselectively provide a fluid flowpath into the other operating componentsof the system being presently described. These fluid transfer tubes maybe of any convenient size necessary to transport the solutions andsolvents to the process unit 10.

Referring to FIG. 2 each of the cartridge receiver tubes 24 comprises abody 28, which is also made from an inert material. In performing theprocesses of the present invention it is critical that sample integritynot be compromised by any contamination leaching out from the body 28when contacted by one or more of the solvents, rinses and othermaterials being used. While many nominally "inert" materials may be usedto make the bodies 28, it has been found that Teflon and polypropyleneare the least sensitive to the various rinses, solvents, and othermaterials used, and are preferred.

Cartridge receiver tube 24 is open at the top, while at the bottom is anoutlet nozzle 30 having a very small orifice therein to permit thesolute or other fluids used to drain therefrom for subsequentcollection, disposal and/or final processing or analysis.

Inside the distal or bottom end of cartridge receiver tube 24 are aseparated pair of inert packing frits 34, mounted across the width ofthe cartridge receiver tube body 28, between which a predeterminedportion of a selected solid extractant or sorbent material 36 isretained. The solid sorbent 36 used is selected specifically to removeone or more particular solutes from a given solution, so a differentextractant must be used when different solvent/solute samples areinvolved. Typical solid sorbents useful in the present invention arealumina (neutral, acidic or basic), silica gel, benzosulfonic acid, andone or more ion exchange resins such as the Amberlite resins obtainablefrom the Rohm and Haas Co. In the embodiment illustrated, changing tubesto meet particular requirements is both simple and relativelyinexpensive. Preloaded cartridge receivers according to the abovedescription can be obtained from Applied Separations, Inc. of Allentown,Pa. Cartridges currently available range from a sorbent volume of about1 ml to about 12 ml with the sorbent quantity ranging from about 100 toabout 1000 mg. The particular one(s) chosen would depend on such factorsas the volume of raw fluid involved and the type and concentration ofthe solute dissolved therein.

When the various cartridge receiver tubes 24 are mounted within thestand 22 and positioned within the processing unit 10 they areeffectively aligned in positions beneath corresponding outlet nozzles 32of standard Luer slip fitting configuration. These nozzles 32 aremounted to the underside of the upper housing extension 12 and fit intothe open top of each corresponding receiving tube 24 mounted within thestand 22. The design serves to close off the relatively large top ofbody 28 and provide a pressurized seal which allows the fluids to beforced through the cartridge receiver tubes 24 when gas pressure isapplied. The seal also provides against airborne or liquid contaminationfrom entering the receiver tubes 24.

Internally, attached to each of these outlet nozzles 32 is a relatedbinary position (on/off) valve (not shown) through which the varioussolutions used are introduced into the receiver tubes 24. Alsoassociated with each of outlet nozzles 32 is a pressure sensing means(also not shown) for sensing the presence or absence of a receivercartridge 24 at a particular position within stand 22 whenever thesystem is placed in operation. The normal operating position of thisvalve is "off" or closed. The valve opens or is "on" only when thepressure sensing means determines there is a cartridge receiver tube 24at that position. Where no cartridge receiver tube 24 is present, thebinary position valve remains in the "off" position so it is notpossible to pass any fluids therethrough, even if the system isprogrammed to do so. This effectively protects the system and overallwork place environment from unintended discharges into the working areaif there is no cartridge receiver tube 24 at a programmed position inthe system.

As noted above, reaction time within the cartridge receiver tubes 24 andthe subsequent discharge of the reactant fluids through outlet nozzle 30is controlled by the ability of the sorbent material to pass the fluidand by a positive gas pressure generated by the process unit 10. Fluidsare retained within the receiver tubes by the hydrophobic property ofthe sorbent and do not flow through the receiver tubes entirely until apositive gas pressure is applied through outlet nozzle 32. Thus,whenever it is required to establish that a certain amount of contacttime occurs to accomplish the particular wash or dissolution operationunderway in the program cycle, positive gas pressure is withheld. A morecomplete explanation of the positive gas pressure, and the method ofapplication and removal follows below. It should be understood that in atotally automated system, all aspects of the system including thegeneration of a positive gas pressure and routing of the input anddischarged fluids would be controlled as a part of the overall systemoperation.

The internal electrical and mechanical configurations of the processunit 10 are shown as FIGS. 3a and 3b, respectively. Central to theoperation of process unit 10 is the programmable controller 50 which isadapted to receive and act upon numerical and functional directionsentered from keypads 16 and 18, as shown in FIG. 3a. Typically, keypad16 is a standard 10 key unit used to enter numerical selections of boththe sample containers 20 and the cartridge receiver tubes 24. Thefunction keypad 18 is used to select operating cycles for a particularoperation of the system.

In one embodiment, the user can select one or more of 6 such cycles. Forconvenience, these have been identified as follows:

(1) the "PROGRAM" cycle, wherein the unit can be directed to dispensethe number of aliquot portions of the raw sample solutions (usually, butnot necessarily, one) and the rinsing agents which are to be taken fromselected sample containers 20 and sent to a preselected group ofcartridge receiver tubes 24 for subsequent use;

(2) the "BATCH" cycle which performs selected process operationsidentically in all of the cartridge receiver tubes 24;

(3) the "RANDOM" cycle which allows the user to specify a particular setof process operations for any or all of the cartridge receiver tubes 24;

(4) the "DRY" cycle wherein a stream of a dry inert gas is appliedthrough outlet nozzle 32 to any or all of cartridge receiver tubes 24for a selected period of time, with the used gases typically beingvented to the outside atmosphere;

(5) the "PURGE" cycle which prepares and clears all process lines forfuture use; and,

(6) the "TEST" cycle wherein the system provides diagnostic means formanually operating each of the individual system components.

It is to be understood that other control systems may be used and whileother functions may also be built into the system to accommodate otherneeds, the six functions described above have been found to besufficient to allow considerable versatility in the operation of thesystem to accommodate a wide variety of process problems. All of theinformation needed by the user to select the mode and scope of operationis presented to him via display driver 52 to alpha-numeric display 14.

It is also understood that other input and output devices, such as acentral computer and/or a video display or printer may augment or besubstituted for the particular control and display units describedabove. Regardless of the control and display system used, once theprogram of operation is selected, the operation continues until all theprogrammed steps are completed.

Conditioning and process solutions are normally stored in and taken fromcontainers 20. As noted, attached to each of these sample containers isone of a plurality of flexible tubes (not shown) which fit throughcontainer cap 20a. These tubes extend essentially to the bottommostportion of said sample containers so as to be able, when required, todraw aliquot portions of the contained fluid therefrom. Each of thetubes is connected at its opposite end to a separate inlet port 56a-56lof a first rotary multi-port valve 58. As shown in FIG. 3b, multi-portvalve 58 has a plurality of inlet positions, in this case 12 in number,and a single outlet port 60. The valve 58 is constructed with aninternal, rotatable central disk portion in which the inlet ports 56a-lare located in a symmetrical fashion around the periphery orcircumference thereof. A selected fluid can only flow through a selectedinlet port 56a-l and the outlet port 60 when the central disk is rotatedto align the outlet with the selected inlet port. Rotation of thecentral disk of the first multi-port valve 58 is accomplished with aprogrammable stepper motor 62, which is set such that an integral numberof steps, i.e. 1, 2, 3, etc. forward, as directed by controller 50, willprecisely move the central disk from one inlet port position to another,as required by the process. That is, each of individual containers 20can be individually accessed merely by rotating the central disk portionof the first multi-port valve 58 until the internal connecting passageof the central disk is opposite the selected one of the inlet ports56a-l, at which time the required fluid, which may be the rawsolute/solvent sample, one or more pre- or post-wash solutions, anelution solution, or any other process solution, can be withdrawn fromthe selected container and started through the desired fluid path.

Fluid movement into and through valve 58 is accomplished with pumpassembly 64, which is comprised of solenoid drive 66 and self-primingpump 68. In a preferred embodiment, the solenoid drive and pump arechosen to effectively cooperate in such a manner that the amount offluid metered into the system from any of the solution containers 20 canbe precisely controlled to within rather close tolerances. In thisembodiment, such effective cooperation is achieved when drive 66 is asolenoid type drive, capable of receiving and reacting to preciseinstructions from the controller 50, and self-priming pump 68 is adiaphragm pump. The system is set up so that when a proper fluid path isestablished through valve 58, operation of the pump system 64 will causea metered amount of the selected fluid to be withdrawn from the selectedone of containers 20 by pump 68 for each pulsed step of solenoid drive66, with said withdrawn fluid then passing through the open path invalve 58 and diaphragm pump 68 and directed through the remainingsegments of the selectable fluid flowpath of the system. Thus, it is thenumber of times the solenoid drive 66 is pulsed which establishes howmuch fluid is withdrawn (metered) and used in any particular operationof the system.

As shown in FIG. 3b, in the embodiment illustrated, the output from pump68 flows through output line 70 into a solenoid controlled 3-way valveassembly 72. The 3-way valve 72 acts as a traffic controller indirecting the fluid flow into the correct path after the appropriateconnections have been established into and through the system. In afirst position of 3-way valve 72, a controlled amount of a selectedfluid (solute or solvent) from a selected solution container 20 ispassed into the inlet port 74 of a second multi-port valve 76 from theoutlet 60 of the first multi-port valve 58. In a second position, a"drying" gas (which may be air or an inert gas such as nitrogen, heliumor carbon dioxide) from inlet line 26 and internal connector line 78 canbe applied through the central inlet port 74 into the interior of valve76. This flow of gas acts to propel any fluid remaining in the inletline 74 of multi-port valve 76 into and through the particular one ofoutlets 80a-80ff which is open at the time, and then assists in thepassage of a solution or solvent through the sorbent material in thecorresponding cartridge receiver tube 24. By so doing, the inlet line iscleared of raw, rinse or wash fluids which might otherwise act ascontaminants in the next operation and thus "dried." This is especiallyimportant if the fluid tends to "wet" the interior walls of the pipingin the system and not flow out. While in the second position, it is alsopossible for the gas pressure to be utilized to discharge residualfluids in the lines through the multi-port valve 76 and out of the unitthrough a fluid discharge line 96, which is described in greater detailin connection with the operation of valve 76. The particular position of3-way valve 72 at any point in the process cycle is controlled by thecontroller 50 according to the specific instructions built into eachprogram cycle.

Referring now to FIGS. 4 and 5, the central portion of a 32 positionmulti-port valve 76 is shown. This valve is the reverse of multi-portvalve 58 in that it has but a single inlet port 74, which receives theoutput of pump 68, and a plurality of outlet ports 80a-ff. It should benoted that output port 80a is normally attached to a discharge line, thepurpose of which will be explained below and that output port 80ff istypically without connection to facilitate a rest or null position. Asshown, the outlet ports 80a-ff are located about the periphery of arotatable disk 82 and are arranged in two concentric circles around thecircumference thereof. As disclosed above, the fluid discharged fromeach of these outlet ports goes into a predetermined one of cartridgereceiver tubes 24 through the associated outlet nozzles 32. Therotatable disk 82 and, more particularly, the rotatable inlet port 74and respective outlet port apertures 80a-ff located on the disk 82 aremaintained in close juxtaposition to the other by a gas balancingpressure to be described more fully below. Positioning of the inlet port74 internal aperture relative to each of the outlet ports 80a-ff invalve 76 is controlled by a programmable stepper motor 84.

A different fluid path between the single inlet port 74 and the outletports is established each time the stepper motor 84 is moved forward bythe controller. The stepper motor 84 controls the movement of centraldisk 82 by attachment of the disk 82 through holes 86a, b to the steppermotor 84. The inlet and outlet port apertures are accurately alignedthrough the use of a photo-illumination/detection pair, operablyconnected through the disk 82 at alignment hole or slot 88, and thestepper motor 84. It will be this signal, the completion of thephoto-illumination and detection link, which indicates the initialposition of the disk 82, i.e. a "home" or rest position. Then thecontroller 50 calculates the number of steps required to reach thedesired outlet port and sends the "count" to the signal interpreter 90with instructions for the programmable stepper motor 84. The motor 84 isthen energized and counts the number of steps required for the disk 82to reach the requested outlet port 80a-ff.

Alternatively, another disk may be placed on the central shaft of thestepper motor 84 having a slot located along its circumference, whichslot is disposed perpendicularly to the point on the circumference. Thephoto-illumination/detection pair can be placed in fixed position oneither side of this disk with the slot serving the identical purpose asthe slot 88 described in connection with disk 82, to create a positionsensing apparatus which indicates a "home" or rest position. Counting bythe controller 50 from the rest position and instructing the steppermotor 84 with a specific "count" to rotate the disk 82 to align theinlet port 74 with the desired outlet port is then efficientlyaccomplished.

The discussion above regarding multi-port valve 76 also applies,generally, to the internal structure of valve 58. Typically, all theactions of both valve motors 62 and 84 are controlled directly by signalinterpreter 90 according to the instructions received from systemcontroller 50.

Returning to the 3-way valve 72, as shown in FIG. 3b, gas line 78 isconnected at its far end to manifold 92. Typically the gas enters themanifold with a pressure of about 25 psi. The outlet pressure into line78 is reduced therein to about 5-7 psi. It is this gas pressure whichacts as the "blow-down" agent propelling and assisting any fluidremaining in the line into the selected cartridge receiver tube 24. Themanifold 92 also applies a gas balancing pressure of about 8-10 psi,provided through line 94, to a chamber behind the rotatable disk 82.This balancing pressure acts as an air spring to force the rotatabledisk 82 against the opposed stationary portion of the multi-port valve76, maintaining the inlet port against, or in close juxtaposition to,the moveable outlet ports arrayed about the disk 82.

At certain times a positive gas pressure is applied to assist in thedischarge of fluids in the cartridge receiver tubes 24. It is theprogrammed application of this positive gas pressure which forces thefluid solutions to flow through the sorbent 36 and the receiver tubeoutlets 30, after the allotted time for the particular reaction involvedhas expired. Of course, where a simple rinse is used or in othersituations where no fluid retention or residence is desired, themanifold 92 and 3-way valve 72 will be instructed to generate (after ashort delay) a positive gas pressure for that receiver tube. Themanifold 92 can also be controlled to provide a vacuum to the system toremove any inert pressurizing or drying gases used, or to exhaust gasesgenerated by chemical reaction within the interconnection tubing andvalve system of the process unit 10 at the conclusion of any particularstep in the process cycle. This is accomplished through the appropriatemanipulation of 3-way valve 72 and the application of a vacuum source toinlet/outlet line 26.

Before the dispensing of a fresh solution through the fluidinterconnection system of the process unit 10 from multi-port valve 58to multi-port valve 76, it is necessary to purge all wetted surfaces ofthe prior fluid solution. Normally, discharge of this undesired fluidwithin any of the fluid lines leading through 3-way valve 72 up to theinput port 74 of the multi-port valve 76 is accomplished by merelypositioning the central disk 82 of the second multi-port valve 76 todischarge into output port 80a. As shown, this output is connected towaste disposal line 96 and a waste receiver container (not shown)through fitting 98. The purge may be assisted through a "blow-down" ofthe fluid lines from the manifold 92, through the 3-way valve 72, andout through the port 80a of multi-port valve 76.

Upon the discharge of eluted fluids from the cartridge receiver tubes24, the waste storage container 100 (contained within stand 22) isreplaced with a purified sample receiver 102 having a correspondingsample container for each cartridge receiver tube location. While thischange can be done manually, it is useful to have the small orifices 30of each receiver tube 24 lead directly into a programmable dual outletmanifold 104 which, under the direction of controller 50, can dischargeinto either container(s) 100 or 102.

It should be understood that each of the selectable inlet ports 56a-l ofthe multi-port valve 58 and each of the selectable outlet ports 80a-ffof the multi-port valve 76 are programmably addressable by controller50. By way of example, consider the connection of inlet port 56h ofmulti-port valve 58 (connected by tubing to the 8th container 20))through the 3-way valve 72 to the outlet port 80q and, consequently, tothe cartridge receiver tube 24 in position 17 on stand 22. This iseasily accomplished by the proper addressing and control of the steppermotors 62 and 84 by controller 50, acting through signal interpreter 90,to rotate the central disks of the two multi-port valves 58, 76 to theselected input and discharge positions creating the desired fluidflowpath. This example is only one of the many different and distinctflow configurations which are possible for individually connecting eachone of the containers 20 to a like, or different (smaller or larger),number of cartridge receiver tubes 24.

OPERATION OF THE SYSTEM

The following is a description of the general series of Steps which areperformed in a "RANDOM" operation of the system of the present inventionin which benzodiazepines are isolated and extracted from urine. For suchan extraction, receiver tubes containing between about 100 and about1000 mg (depending on sample size) of Octadecyl (C18) as solid sorbent36 are used.

STEP 1: From the menu of possible program options as defined above, theoperator selects and enters from the function keyboard 18 the choice ofthe "RANDOM" cycle.

STEP 2: The operator then selects and enters from the number keypad 16the assigned number or numbers for each of the selected cartridgereceiver tubes 24 to which the process solutions are to be sent.

STEP 3: Next the operator selects and enters the number of the firstprocess container 20 to be addressed and then the amount of solutionwhich is to be metered from said container for each of the selectedcartridge receiver tubes 24.

In normal operation, the input solution selections include, in additionto introducing the sample being tested, various solutions used topre-condition the sorbent, wash the sorbent/solute combination, elutethe solute, and clean out and recondition the system before the nexttest cycle option is chosen and performed.

In the instant example, the solid sorbent 36 in the selected one(s) ofcartridge receiver tubes 24 is pre-conditioned with a methanol wash(solution 1) and then with an 0.1M sodium carbonate solution (solution2). An aliquot sample of each raw test sample solute/solvent solution isthen placed in the cartridge receiver tubes 24 (either by independentlypippetting or automatic metering from a selected container 20) andpassed through the sorbent to selectively remove the solute therefrom.The extracted solute is washed to remove any residual raw solution orother contaminants remaining on the extracted solute with a mixturecomprising 85 vol % 0.1M sodium carbonate/15 vol % acetonitrile(solution 3), and eluted with methanol. Prior to use, the pH of the rawsolute/solvent sample materials is adjusted to about 10.5 with a pHadjusting amount of solution 2.

STEP 4: Step 3 is repeated as often as necessary to complete the finalextraction, purification and elution of the desired solute.

STEP 5: The operator then starts the program, at which time the systemautomatically accomplishes the following:

a. the solid sorbent material is pre-conditioned with 2 aliquots of 3 mlsolution 1, followed immediately by 3 ml of solution 2;

b. 10 ml of the prepared sample solution is then passed through thesorbent in each of the selected one(s) of cartridge receiver tubes 24;

c. the material extracted from the sample solution is then washed withtwo sequential 0.6 ml volumes of solution 3, said solvent being retainedwithin the plurality of cartridge receiver tubes 24 for a sufficientamount of time to remove any impurities from the extracted solute.

In an automated system, the solutions used in Steps 5a-c would either beautomatically directed to suitable waste storage containers forsubsequent disposal through dual outlet manifold 104 into container 100,or manually collected and discarded. Since the volume of each solutionused in this operation tends to be rather small, the hazards resultingfrom such temporary storage tends to be rather minimal.

At the conclusion of Steps 5a-c, the final recovery step is accomplishedby washing the extractant material with 2 sequential 0.6 ml volumes ofsolution 1, with the solvent being retained within the receiver tube 24for a sufficient length of time to fully dissolve and remove the solutefrom solid sorbent 36. In its most basic embodiment, the system isadapted to stop at this point and emit either an aural or visual signalthat the waste receiver 100 should be disconnected and replaced with thepurified sample container 102 for the eluted solution. In a somewhatmore advanced embodiment (illustrated in FIG. 7) the dual outletmanifold 104 can be directed by programmable controller 50 to dischargeeither into waste storage container 100 or into purified samplecontainer 102, from which the final sample can be taken for analysis orother use. The general scheme of the steps described above isillustrated in FIG. 6. For the example to obtain benzodiazepines, theabove procedure produces a final methanol solution suitable forimmediate analysis without additional processing. For otherapplications, it may be necessary to evaporate the eluted solvent toeither recover the solute as a solid or to reconstitute the solute in adifferent solvent.

In an alternative embodiment, as shown in FIG. 7, controller 50comprises a computer 106 having as an integral part thereof anassociated programmable read-only-memory (PROM) to assume control, incombination with a central processing unit, over the various functionsof the operable elements of system 10. Monitoring and control of theseelements is accomplished through a set of fixed parameters containedwithin the PROM operating in conjunction with a set of instructionssupplied by the system operator through the computer keyboard 108. Thesepre-programmed PROM factors include such items as the quantity of fluidper pulse applied to solenoid drive 66 and, therefore, the total numberof pulses required to extract and meter a selected quantity of fluidfrom a selected one of solution containers 20, the number of pulsesrequired to move the central disks of the two multi-port valves in thesystem to move from one inlet (or outlet) port to the next availableposition, the solute hold time within a selected cartridge receiver tube24 for each given procedure, and the "blow-down" time for clearing thedevice of fluid after a given procedure is completed.

Communication between system 10 and the computer 106 is through anintegral RS232 communications port 110 and device status and otherinformation as needed are displayed on a video monitor 112. Thiscombination not only provides a versatile alternative to alpha-numericdisplay 14 and keypads 16 and 18 but allows the system operatinginstructions to be setup, monitored, modified and controlled from acentral or remote location. Other capabilities available to the systemoperator are those of creating new procedures when required, changingthe default parameters stored in the PROM for a given procedure,changing the report options and aborting the program at the operator'soption.

Typically, the options and procedures are presented in menu form, thusallowing the easy selection of operations such as the number of aliquotsdesired, the flow rate of each solution used, the hold time after asolution dispensing operation is completed, and the gas dry time whichthe operator desires to have performed. Further, the software usedprovides the ability to enter a number of record keeping items such asthe title of the overall operation being performed, e.g "STEROIDS FROMURINE" or "PCB's FROM WATER," and the identification of each of thereceiver cartridges 24, and of the sorbent material 36 used. Thesecapabilities are especially valuable when toxic, flammable, radioactiveor otherwise hazardous materials are involved, or a plurality ofoperating systems must be controlled.

To facilitate this overall control, the process unit 10 may furthercomprise position indicators such as one or more position encodersincorporated onto multi-port valves 58 and 76. The position encodersprovide a unique signal which identifies each input or output connectionpoint. Also, there can be incorporated with each of these valves aposition sensor to establish an exact position for the rotating centraldisk sections of the multi-port valves at the start of a givenprocedure. This is required since, usually, each "step" of the motors 62and 84 requires more than one step pulse to move the inlet (outlet) fromone "flow-through" position to another. The sensor may be aphoto-illumination and detection pair placed on the periphery of therotor and stator units of the valves.

In one mode of operation, at the start of operation, the sensors respondto a position inquiry from the computer by causing both of the valverotors to move to an initial starting point, or "home" position, whichis established when the photo-illuminator and detector line up. At thestart of a given procedure, once this starting position has beenreached, the computer 106 provides a signal to restart motor drive 62and the number and polarity of the pulses required to cause the centralrotor of valve 58 to move from this "home" position to the first fluidinput location and establish the fluid flowpath for the selection.Thereafter, the computer monitors the position of the motor driven rotorby keeping track of the number of pulses generated to move the rotor toits present position. Where more than one process solution is to beused, it computes and then, at the proper time, transmits the number andpolarity of the steps needed to move the central rotor forward to thenext selected solution container location. Similar signals are sent toinitially position and then move the second multi-port valve motor 84.

In an alternative embodiment, home positioning of the valve rotors isassumed at the conclusion of a test run by having the position signalinterpreter 90 count down to zero from whatever number represents thefinal operational positions of the valve rotors. This would move themotor driven rotors back to "home," which, typically, is at an openinlet on valve 58 or position 80ff on valve 76.

The control signals sent to solenoid drive 66 come directly fromcontroller 50 and give the number of pulses required to cause the pumpto withdraw the desired amount of fluid from the selected samplecontainer 20 and then pump it into the system. For this operation, noprepositioning of a rotatable member is required.

At the start of operation, the computer 106 also polls each of thereceiver cartridge tube locations to detect the presence or absence of acartridge tube at each output location. The absence of a "cartridgepresent" signal from the cartridge sensing means associated with each ofthe valves connected to outlet nozzles 32 will cause the computer topermanently "lock-off" that position so that no fluid can be pumpedthereto. This lock will remain in effect so long as no cartridgereceiver tube 24 is placed and detected at that position and willsupersede an operator's instruction to the contrary.

The control and status of all operating devices are polled andcontrolled by the computer 106 through a standard interface usingdigital-to-analog and analog-to-digital signal conversion and standardcommunication techniques. Once a procedure is started, the computercontrols the starting position, movement and final positions of bothrotary valves 58, 76, the pumping time of pump assembly 64, theactuation and positioning of 3-way valve 72, the generation and releaseof gas pressures, blow down and/or venting of the system, etc. and allother operating and condition features of the present invention. Withthis degree of control, it is now possible to individually control or"batch" process each of the receiver cartridge tubes 24 so that set upand performance of a variety of different fluid treatment processes iseasily accomplished.

A basic display screen as used in conjunction with monitor 112 is shownin FIG. 8. This provides the system operator with a degree of flexiblesystem control and management not possible with the sequencedinstruction dependent alpha-numeric display and keypads used with thebasic embodiment described above. For example, the computer 106 andaccompanying screens viewable on the monitor 112 give the operator thepower to alter or modify one or a number of control parametersapplicable to a given portion (or all) of a particular test procedure,with the operating system defaulting to the test parameter instructionsin the PROM only if no further entry is made. The monitor 112 alsodisplays the status of each step in the operational procedure selected,and provides the ability to better identify test samples by requiringunique identification means on each of the cartridge receiver tubes 24and then reading these unique cartridge receiver tube identifiers fromeach of the individual tubes (in the form of "bar-codes") with a lightwand (or other "bar-code" reader means) as they are placed at aparticular position on stand 22. At the conclusion of the operatingprocedure, the monitor 112 provides the operator a summary of theamounts and types of test solutions used for inventory control. Displayscreens showing an example procedure involving one methanolconditioning, one water wash and two NaOH elution cycles are shown inFIGS. 9a-d. Lastly, a display screen giving the locations of thesolution containers 20 containing these solutions is presented as FIG.10. The computer 106 also permits reports of the solid phase extractionand elution procedure to be printed on an associated printer forretention with the actual test samples.

It will be understood that various changes in the details, materials,and arrangement of the parts which have been described and illustratedin order to explain the nature of the invention, may be made by thoseskilled in the art without departing from the spirit and principles ofthe invention, and accordingly, reference should be made to appendedclaims, rather than to the foregoing specification, as indicating thescope of the invention.

What is claimed is:
 1. A method for extracting one or more particularsolutes from a sample solution, said method comprising the steps of:a.placing an amount of said sample solution into a non-contaminatingreceptacle, said receptacle being operatively connected to means adaptedto meter predetermined amounts of said solution therefrom; b.programmably introducing at least one metered amount of said samplesolution into a selected one or more of a plurality of cartridgereceiver tubes, each of said selected receiver tubes containing anamount of the same or a different solid phase extractant or sorbentthrough which said solution will pass, said sorbent being selected toremove substantially all of one of said particular solutes from saidsample solution; c. programmably introducing into said selected receivertubes a predetermined amount of one or more solvents to pass throughsaid sorbent, said solvents being adapted to selectively dissolve andremove substantially all of any residual sample solution and residualcontaminants remaining on or absorbed by said sorbent while permittingsubstantially all of said particular solute to remain; d. programmablyintroducing into said selected receiver tubes one or more predeterminedamounts of at least one solvent to pass through said sorbent andselectively form a contamination-free solution with a selected one ofsaid particular solutes resident therein; and e. removing saidcontamination-free solution from said selected receiver tubes forfurther use.
 2. The method of claim 1 wherein the sequential order andamounts of said metered solutions are controlled by a programmablecontrol means.
 3. The method of claim 1 wherein the steps ofsequentially introducing selected solutions is controlled by aprogrammable selection means and the quantitative transfer of saidsolutions is performed by programmable pump means and valve means. 4.The method of claim 1 further comprising the step of introducing intosaid receiver tubes and passing through said sorbent an amount of one ormore conditioning solutions before the introduction of the samplesolution into the receiver tubes.
 5. The method of claim 1 furthercomprising the step of flushing the fluid connection between a pluralityof inlet ports of a first multi-port valve means and individual stopvalves connected to each of the plurality of outlet ports of a secondmulti-port valve means which connect the sample receptacle and selectedsolution receptacles to the plurality of cartridge receiver tubes toremove any contaminants from solution residues.
 6. The method of claim 1further comprising the step of drying the fluid connection between aplurality of inlet ports of a first multi-port valve means andindividual stop valves connected to each of the plurality of outletports of a second multi-port valve means which connect the samplereceptacle and selected solution receptacles to the plurality ofcartridge receiver tubes to remove any contaminants from solutionresidues.
 7. A method for extracting one or more particular solutes froma sample solution, said method comprising the steps of:a. placing anamount of said sample solution into at least a selected one of aplurality of cartridge receiver tubes, each of said receiver tubescontaining an amount of the same or a different solid phase extractantor sorbent through which said solution will pass, said sorbent beingselected to remove substantially all of one of said particular solutesfrom said sample solution; b. programmably introducing into saidselected receiver tubes a predetermined amount of one or more solventsto pass through said sorbent, said solvents being adapted to selectivelydissolve and remove substantially all of any residual solution andresidual contaminants remaining on or absorbed by said sorbent whilepermitting substantially all of said particular solute to remain; c.programmably introducing into said selected receiver tubes one or morepredetermined amounts of at least one solvent to pass through saidsorbent and selectively form a contamination-free solution with aselected one of said particular solute resident therein; and d. removingsaid contamination-free solution from said selected receiver tubes forfurther use.
 8. The method of claim 7 wherein the sequential order andamounts of said metered solutions are controlled by a programmablecontrol means.
 9. The method of claim 7 wherein the steps ofsequentially introducing selected solutions is controlled by aprogrammable selection means and the quantitative transfer of saidsolutions is performed by programmable pump means and valve means. 10.The method of claim 7 further comprising the step of introducing intosaid receiver tubes and passing through said sorbent an amount of one ormore conditioning solutions before the introduction of the samplesolution into the receiver tubes.
 11. The method of claim 7 furthercomprising the step of flushing the fluid connection between a pluralityof inlet ports of a first multi-port valve means and individual stopvalves connected to each of the plurality of outlet ports of a secondmulti-port valve means which connect the sample receptacle and selectedsolution receptacles to the plurality of cartridge receiver tubes toremove any contaminants from solution residues.
 12. The method of claim7 further comprising the step of drying the fluid connection between aplurality of inlet ports of a first multi-port valve means andindividual stop valves connected to each of the plurality of outletports of a second multi-port valve means which connect the samplereceptacle and selected solution receptacles to the plurality ofcartridge receiver tubes to remove any contaminants from solutionresidues.